Abstract 67P
Background
Promising clinical activity has been reported in patients with MET-altered NSCLC treated with tepotinib, an oral, selective, potent MET tyrosine kinase inhibitor. To support clinical development, we aimed to further characterize the safety profile of tepotinib in patients with cancer.
Methods
In this analysis from 5 phase I and II studies of tepotinib administered 500 mg once daily, adverse events (AEs), graded by NCI CTCAE v4.03, were pooled and summarized for all patients and for the subgroup of Asian patients.
Results
As of 28 Sep 2018, 228 patients (81 [35.5%] Asian, 59 [25.9%] NSCLC, 121 [53.1%] HCC) had received tepotinib 500 mg/day for a median of 2.7 months (range 0–21.5); in the ongoing phase II VISION study (NCT02864992), median was 4.1 months. The most common treatment-related AE of any grade was peripheral edema occurring in 33.8% of patients overall and in 24.7% of Asian patients. Other common treatment-related AEs were diarrhea, fatigue, and nausea (Table). Dose reduction due to an AE regardless of causality occurred in 33 (14.5%) patients and discontinuation in 49 (21.5%) patients; peripheral edema led to a dose reduction in 12 (5.3%) patients and discontinuation in 7 (3.1%) patients. In the Asian population, 13 (16.0%) patients had a dose reduction and 13 (16.0%) patients discontinued due to an AE; peripheral edema led to a dose reduction in 4 (4.9%) Asian patients and to no discontinuations. Two AEs leading to death were considered by the investigator to be potentially treatment-related and occurred in patients with HCC (upper gastrointestinal hemorrhage [in an Asian patient] and hypoglycemic coma).Table: 67P
All patients (N = 228) | Asian patients (N = 81) | |||
---|---|---|---|---|
Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | |
Treatment-related AE (≥10%), n (%) | 172 (75.4) | 52 (22.8) | 64 (79.0) | 26 (32.1) |
Peripheral edema | 77 (33.8) | 8 (3.5) | 20 (24.7) | 0 |
Diarrhea | 45 (19.7) | 4 (1.8) | 27 (33.3) | 4 (4.9) |
Fatigue | 34 (14.9) | 3 (1.3) | 14 (17.3) | 3 (3.7) |
Nausea | 29 (12.7) | 0 | 9 (11.1) | 0 |
Decreased appetite | 27 (11.8) | 0 | 12 (14.8) | 0 |
Blood creatinine increased | 18 (7.9) | 1 (0.4) | 11 (13.6) | 0 |
Hypoalbuminemia | 16 (7.0) | 1 (0.4) | 10 (12.3) | 0 |
Amylase increased | 13 (5.7) | 4 (1.8) | 9 (11.1) | 2 (2.5) |
Conclusions
Tepotinib demonstrated an acceptable safety profile in patients with advanced cancer, with a similar profile in Asian patients and in the overall population. Further characterization of the clinical relevance of peripheral edema is ongoing.
Clinical trial identification
NCT01014936, NCT01832506, NCT01988493, NCT02115373, NCT02864992.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Jen Lewis, PhD of Bioscript Science (Macclesfield, UK).
Legal entity responsible for the study
Merck KGaA.
Funding
Merck KGaA.
Disclosure
K. Yamazaki: Honoraria (self): Chugai; Honoraria (self): Takeda; Honoraria (self): Yakult; Honoraria (self): Daiichi‐Sankyo; Honoraria (self): Merck Serono; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Bayer; Honoraria (self): Eli Lilly; Honoraria (self): Taiho; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. P.K. Paik: Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Honoraria (self): Takeda. R. Veillon: Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Merck. T. Decaens: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Travel / Accommodation / Expenses: Gilead; Honoraria (self), Travel / Accommodation / Expenses: AbbVie; Honoraria (self): Sanofi; Advisory / Consultancy: BTG; Advisory / Consultancy: Sirtex; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Merck Serono; Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Genoscience Pharma. S. Faivre: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Blueprint; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. G.S. Falchook: Licensing / Royalties: Wolters Kluwer; Advisory / Consultancy, Travel / Accommodation / Expenses: Fujifilm; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Millennium; Speaker Bureau / Expert testimony: Total Health Conferencing ; Research grant / Funding (institution): 3-V Biosciences; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): ADC Therapeutics; Research grant / Funding (institution): Aileron; Research grant / Funding (institution): American Society of Clinical Oncology; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): ARMO; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bioatla; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ciclomed, Curegenix, Curis, DelMar, eFFECTOR, Eli Lilly, Exelixis, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, Ignyta, Incyte, Jacobio, Jounce, Kolltan, Loxo, MedImmune, Millennium, Merck, miRNA Therapeutics, National Institutes of Health, No. J. Scheele: Full / Part-time employment: Merck KGaA. R. Bruns: Full / Part-time employment: Merck KGaA. K. Berghoff: Full / Part-time employment: Merck KGaA. All other authors have declared no conflicts of interest.
Resources from the same session
64P - Entrectinib in locally advanced/metastatic ROS1 and NTRK fusion-positive non-small cell lung cancer (NSCLC): Updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Filippo de Braud
Session: Poster display session
Resources:
Abstract
65P - Updated efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Christian Rolfo
Session: Poster display session
Resources:
Abstract
66P - Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
Presenter: Matthew Krebs
Session: Poster display session
Resources:
Abstract
68P - A novel anti-EGFR antibody HLX07 for potential treatment of squamous cell carcinoma of the head and neck
Presenter: Ming Mo Hou
Session: Poster display session
Resources:
Abstract
69P - Irinotecan and cisplatin therapy-induced neutropenia as a prognostic factor in patients with extensive-disease small cell lung cancer
Presenter: Hiroshi Ishikawa
Session: Poster display session
Resources:
Abstract
70P - Is safe and efficient by intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for cholecystolithiasis combined with common bile duct stones: A meta-analysis
Presenter: Jiasheng Cao
Session: Poster display session
Resources:
Abstract
71P - Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer: A propensity score analysis
Presenter: Chaobin He
Session: Poster display session
Resources:
Abstract
72P - Novel technique of near-focus mode for accurate operation during endoscopic submucosal tunneling procedure: A two-center comparative study
Presenter: Wei Peng
Session: Poster display session
Resources:
Abstract
73P - Cabozantinib in combination with anti-PD1 immune checkpoint inhibitor in syngeneic tumour mouse models
Presenter: Rachel Sparks
Session: Poster display session
Resources:
Abstract
74TiP - Phase I study of BI 836880, a VEGF/Ang2-blocking nanobody®, as monotherapy and in combination with BI 754091, an anti-PD-1 antibody, in Japanese patients (pts) with advanced solid tumours
Presenter: Kentaro Yamazaki
Session: Poster display session
Resources:
Abstract